Our objectives are to determine if the accumulation of catalytically incompetent enzyme forms in senescent organisms can be related to age-dependent alterations in their rates of turnover. Available evidence indicates that total protein turnover is severely impaired in old nematodes (Turbatrix aceti), and that the appearance of structurally-altered enolase molecules in aged T. aceti may result from a decrease in their rate of degradation. A similar age-associated decline in subcellular protein degradation has been demonstrated in Fischer 344 rats; distinct patterns of turnover have been observed which depend on the tissue examined. We plan to continue to study turnover rates of aberrant enzymes in senescent nematodes and rats; results will be compared with: degradation half-lives determined for enzymes which do not undergo deleterious modification with advancing age. We have further identified two families of proteinases in T. aceti, one active in the acid region and the other in the alkaline pH range. We propose to isolate and characterize these proteases, to determine their subcellular location, and to investigate their possible roles in nematode protein catabolism and aging.